Abstract | AIMS: Previous studies showed that natural prenyloxyphenylpropanoid derivatives have potent biological properties in vivo. Given the structural similarities between these compounds and known peroxisome proliferator-activated receptor ( PPAR) agonists, the present study examined the hypothesis that propenoic acid derivatives activate PPARs. MAIN METHODS: Chimeric reporter assays were performed to identify propenoic acid derivates that could activate PPARs. Quantitative polymerase chain reaction (qPCR) analysis of wild-type and Pparbeta/delta-null mouse primary keratinocytes was performed to determine if a test compound could specifically activate PPARbeta/delta. A human epithelial carcinoma cell line and primary mouse keratinocytes were used to determine the effect of the compound on cell proliferation. KEY FINDINGS: Three of the propenoic acid derivatives activated PPARs, with the greatest efficacy being observed with prenyloxycinnamic acid derivatives 4'-geranyloxyferulic acid (compound 1) for PPARbeta/delta. Compound 1 increased expression of a known PPARbeta/delta target gene through a mechanism that requires PPARbeta/delta. Inhibition of cell proliferation by compound 1 was found in a human epithelial carcinoma cell line. SIGNIFICANCE:
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Authors | Salvatore Genovese, Jennifer E Foreman, Michael G Borland, Francesco Epifano, Frank J Gonzalez, Massimo Curini, Jeffrey M Peters |
Journal | Life sciences
(Life Sci)
Vol. 86
Issue 13-14
Pg. 493-8
(Mar 27 2010)
ISSN: 1879-0631 [Electronic] Netherlands |
PMID | 20153754
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Coumarins
- PPAR delta
- PPAR-beta
- Phenylpropionates
- aurapten
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Topics |
- Animals
- COS Cells
- Cell Line
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Chlorocebus aethiops
- Coumarins
(chemistry, pharmacology)
- Gene Expression Regulation
(drug effects)
- Humans
- Mice
- Molecular Structure
- PPAR delta
(metabolism)
- PPAR-beta
(metabolism)
- Phenylpropionates
(chemistry, pharmacology)
- Polymerase Chain Reaction
- Up-Regulation
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